Introduction
Secukinumab is a human monoclonal antibody that selectively inhibits interleukin-17A (IL-17A), a pro-inflammatory cytokine involved in chronic inflammatory and autoimmune diseases. By blocking IL-17A, it reduces inflammation and helps normalize affected tissues, particularly in the skin and joints. Secukinumab is used to treat plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and other IL-17-mediated inflammatory conditions, where it has demonstrated high efficacy in reducing disease activity and improving clinical outcomes.
Uses
Secukinumab is an immunomodulating agent and interleukin antagonist used to manage moderate to severe plaque psoriasis and active psoriatic arthritis or ankylosing spondylitis.
For the treatment of moderate to severe plaque psoriasis in patients that are candidates for systemic therapy or phototherapy.
Associated Conditions
Mechanism of Action
Secukinumab is a human monoclonal antibody that targets IL-17A cytokine to downregulate inflammation in psoriasis, an autoimmune dermatological disease. The pathophysiology of psoriasis has not been fully established, however it is known that dysregulation of innate and adaptive immune responses plays part in the chronic inflammation associated with the disease. IL-17 represents is a six-membered family (IL-17A to F) of pleiotropic pro-inflammatory cytokines, expression of which is found to be elevated in psoriatic skin. These cytokines act on many different cell types and provide defense against different extracellular pathogens causing fungal or bacterial infections. IL-17 cytokines are produced by many cells involved in immune system defense, such as Th17, mast cells, neutrophils, and dendritic cells - all implicated in promoting inflammation. There is evidence linking IL-17 to pathogenesis of multiple autoimmune diseases including rheumatoid arthritis, spondyloarthritis, psoriasis, Crohn's disease, multiple sclerosis, and even atherosclerosis.
Absorption
Bioavailability after subcutaneous administration was 55-77%.
Volume of Distribution
Volume of distribution (Vd) in interstitial fluid of skin (+/- psoriasis) was 27-40% of that in serum after single subcutaneous dose of 300 mg. Vd increased at higher body weights.
Half Life
22-31 days
Clearance
Serum clearance was increased with higher body weights.
Food Interactions
No interactions found.
Dosage
1. Recommended dosage is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. For some patients, a dose of 150 mg may be acceptable.
Psoriatic Arthritis-
1. For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, use the dosage and administration for plaque psoriasis.
2. For other psoriatic arthritis patients administer with or without a loading dosage. The recommended dosage:
- With a loading dosage is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter
- Without a loading dosage is 150 mg every 4 weeks
- If a patient continues to have active psoriatic arthritis, consider a dosage of 300 mg.
Ankylosing Spondylitis-
1. Administer with or without a loading dosage. The recommended dosage:
- With a loading dosage is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter
- Without a loading dosage is 150 mg every 4 weeks
